One of the major functions of the kidney is to produce ammonia for the excretion of hydrogen ions and thereby regulate acid-base balance. Recently, a new metabolic cycle for the production of ammonia--the purine nucleotide cycle--was discovered in extracts of muscle. In light of our encouraging pilot studies that demonstrate the presence of the purine nucleotide cycle in the kidney, we wish to assess the function and significance of the cycle in renal ammonia production. We wish to 1) describe the purine nucleotide cycle in the kidney--its location in different regions of the kidney, its presence in different species, including dog and man, and the optimum experimental conditions for its determination, and 2) assess the importance of the cycle in the regulation of ammonia production during acidosis, alkalosis, renal failure, and other conditions of altered ammonia production. The kidneys from animals under conditions of altered ammonia production will be studied to assess the physiological role of the purine nucleotide cycle. We will also study the isolated perfused kidney from rats who have increased, normal, or decreased renal ammonia production. Our long term objective is to discover the controlling mechanisms of ammonia production in the kidney and to determine how the production of ammonia can be regulated in the treatment of disorders of acid-base balance.